CD28 superagonist-mediated boost of regulatory T cells increases thrombo-inflammation and ischemic neurodegeneration during the acute phase of experimental stroke

نویسندگان

  • Michael K Schuhmann
  • Peter Kraft
  • Guido Stoll
  • Kristina Lorenz
  • Sven G Meuth
  • Heinz Wiendl
  • Bernhard Nieswandt
  • Tim Sparwasser
  • Niklas Beyersdorf
  • Thomas Kerkau
  • Christoph Kleinschnitz
چکیده

While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

O10: Thrombo-Inflammation in Acute Ischemic Stroke

Ischemic stroke has been classified as a merely thrombotic disease, so the main goal of its treatment is the recanalization of the occluded vasculature. However, despite fast restoration of blood circulation, progressive stroke still develops in many patients, which has led to the concept of reperfusion injury.  The underlying mechanism is only partly known. Though, it is accepted now, tha...

متن کامل

Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis

CD4+CD25+ regulatory T cells (T reg cells) play a key role in controlling autoimmunity and inflammation. Therefore, therapeutic agents that are capable of elevating numbers or increasing effector functions of this T cell subset are highly desirable. In a previous report we showed that a superagonistic monoclonal antibody specific for rat CD28 (JJ316) expands and activates T reg cells in vivo an...

متن کامل

T Regulatory Cells Frequency During Maintenance Phase Chemotherapy for Pediatric Acute Lymphoblastic Leukemia

Background: Drugs used in cancer treatment specifically kill T regulatory cells. Objective: To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL). Materials: We evaluated the percentages of regulatory T cells by flow cytometry. Soluble CTLA-4 (sCTLA-4) ...

متن کامل

Amplification of Regulatory T Cells Using a CD28 Superagonist Reduces Brain Damage After Ischemic

Post-ischemic neuroinflammation is viewed as a promising target in ischemic stroke because inflammatory mechanisms contribute substantially to secondary brain damage. The postischemic inflammatory response includes mechanisms of innate and adaptive immunity. Innate immune cells, such as microglia and macrophages, are activated and secrete proinflammatory cytokines, including interleukin (IL)-1 ...

متن کامل

Numerical status of CD4+CD25+FoxP3+ and CD8+CD28- regulatory T cells in multiple sclerosis

Objective(s): Regulatory T cells, including CD4+CD25+Fox3+ and CD8+CD28- cells play an important role in regulating the balance between immunity and tolerance. Since multiple sclerosis is an inflammatory autoimmune disease, regulatory T cells are considered to be involved in its pathogenesis. In this study, we investigated the circulatory numbers of the two mentioned types of regulatory T cells...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 35  شماره 

صفحات  -

تاریخ انتشار 2015